Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use

• US 8,481,073 B2
• Filed: 10/24/2011
• Issued: 07/09/2013
• Est. Priority Date: 04/28/2004
• Status: Active Grant

• Current Assignee: Angiodevice International GmbH (Angiotech Pharmaceuticals (US), Inc.)
• Original Assignee: Angiodevice International GmbH (Angiotech Pharmaceuticals (US), Inc.)
• Inventors: Daniloff, George Y., Sehl, Louis C., Trollsas, Olof Mikael, Schroeder, Jacqueline A., Gravett, David M., Toleikis, Philip M.
• Primary Examiner(s): Roberts, Lezah
• Assistant Examiner(s): Liu, Tracy
• Application Number:
  US13/279,982
• Publication Number:
  US 20120039980A1
• Time in Patent Office: 624 Days
• Field of Search: 424/484, 514/19.1
• US Class Current: 424/442
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Methods of preventing adhesion between issues are provided that utilizes in situ crosslinked biomaterials. The biomaterial contains at least the crosslinked product of two biocompatible, non-immunogenic components having reactive groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. Exemplary uses for the crosslinked compositions include preventing adhesions following surgery or injury, and preventing scar tissue formation.

Claims

1. A method of preventing adhesions between tissues of a patient, comprising:

(a) providing a dry powder composition including;

i. a first component having a first hydrophilic polymer core substituted with m thiol groups, where m≧

2; and

ii. a second component having a second hydrophilic polymer core substituted with n electrophilic groups, where n≧

2 and m+n>

4, and wherein the electrophilic group is independently —

(CO)—

O—

(CO)—

R (where R is an alkyl group), CH═

CH—

CH═

O, —

CH═

CH—

C(CH₃)═

O, —

N═

C═

O, —

N═

C═

S, —

SO₂CH═

CH₂, —

O(CO)—

C═

CH₂, —

(CO)—

C(CH₃)═

CH₂, —

S—

S—

(C₅H₄N), —

O(CO)—

C(CH₂CH₃)═

CH₂, —

CH═

CH—

C═

NH, —

COOH, —

(CO)O—

N(COCH₂)₂, —

O—

(CO)—

O—

N(COCH₂)₂, —

CHO, —

(CO)O—

N(COCH₂)₂—

S(O)₂OH, and —

N(COCH)₂;

(b) rendering the nucleophilic and electrophilic groups reactive by exposing the composition to an aqueous environment to effect inter-reaction;

wherein said exposure comprises;

(i) dissolving the dry powder composition in a first solution having a pH within the range of about 2.1-2.3 to form a homogeneous solution, and

(ii) adding a second solution having a pH within the range of about 6.0 to 11.0 to the homogeneous solution to form a mixture; and

(c) placing the mixture into contact with tissue and allowing a three-dimensional composition to form on the tissue.

2. The method of claim 1, wherein the first hydrophilic polymer core and the second hydrophilic polymer core are independently a linear, branched, dendrimeric, hyperbranched, or star polymer.

3. The method of claim 2, wherein the first hydrophilic polymer core and the second hydrophilic polymer core are independently selected from polyalkylene oxides;

polyols;

poly(oxyalkylene)-substituted diols and polyols;

polyoxyethylated sorbitol;

polyoxyethylated glucose;

poly(acrylic acids), analogs and copolymers thereof;

polymaleic acids;

polyacrylamides;

poly(olefinic alcohols);

poly(N-vinyl lactams);

polyoxazolines;

polyvinylamines; and

copolymers thereof

4. The method of claim 3, wherein the first hydrophilic polymer core and the second hydrophilic polymer core are independently a polyalkylene oxide or a polyol selected from polyethylene glycol and poly(ethylene oxide)-poly(propylene oxide) copolymers.

5. The method of claim 4, wherein the hydrophilic polymer is a poly(oxyalkylene)-substituted polyol, wherein the polyol is selected from mono-, di- and tri-polyoxyethylated glycerol, mono- and di-polyoxyethylated propylene glycol, mono- and di-polyoxyethylated trimethylene glycol, and pentaerythritol.

6. The method of claim 1 further comprising delivering a biologically active agent with the mixture.

7. The method of claim 6, wherein the biologically active agent is a part of the dry powder composition.

8. The method of claim 6, wherein the biologically active agent is a part of the first solution.

9. The method of claim 6, wherein the biologically active agent is a part of the second solution.

10. The method of claim 6 wherein the biologically active agent is an anti-fibrotic agent.